Isolated large (800 Angstrom Units) dense-core vesicles can now be prepared at a routine purity of 80-90% entirely comparable to that for adrenomedullary vesicles. A combined biochemical, pharmacological and ultrastructural approach is employed to study the characteristics of the large dense-core vesicles, both isolated and in situ. Properties of the vesicles will be studied during maturation and proximo-distal transport. The differential effects of pharmacological agents and others on the newly discovered fast release pool of norepinephrine will be studied. Particular emphasis will be placed on 'stabilizers' and 'labilizers' of the norepinephrine fast and slow release pools, dopamine Beta-hydroxylase activity and release, false transmitters and others. The possible relationships of the large dense-core vesicles to the smaller (450 Angstrom Units) dense-core vesicles will be sought, both in isolated preparations and in situ. Generally accepted, but invalid dogmas, such as the 4:1 ratio of norepinephrine: ATP in adrenergic nerve vesicles; proportional release of norepinephrine, ATP and dopamine Beta-hydroxylase from these vesicles; and analogies presumed from data on adrenomedullary vesicles will be vigorously exposed.